Photochemical methods are unique because (1) they enable the synthesis of unusual, strained molecular frameworks that cannot be synthesized by other methods, and (2) they use light, which is cleaner, less expensive, and more renewable than conventional chemical reagents. Nevertheless, pharmaceutical companies rarely take advantage of photochemical synthesis because the need for specialized photochemical equipment is an impractical impediment and because very few methods to control the stereochemistry of photochemical reactions exist. Therefore, the structures of the molecules that are produced by photochemical synthesis have essentially not been examined as possible drug candidates. This Proposal describes an innovative new strategy to perform photochemical reactions using readily available sources of visible light such as a consumer light bulb or ambient sunlight instead of a specialized photochemical reactor. Research will proceed in two phases: 1. Development of a photocatalytic system that is able to efficiently convert visible light energy into chemical reactivity with high levels of stereochemical control. 2. Application of this system to a variety of new chemical reactions that produce unusual molecular structures. These methods are powerful, robust, and simple to perform on large, industrially relevant scales. Thus, the research described in this proposal will significantly impact both the academic chemistry community and the broader community of medicinal chemists who require new methods of molecule construction to discover the next generation of life-saving drugs. PUBLIC HEALTH RELEVANCE: The function of a drug is determined by its structure, and drugs with similar structures tend to have similar effects on human disease. The discovery of new drugs that could treat currently incurable diseases, therefore, relies upon the ability of chemists to construct different kinds of molecules that differ significantly in structure from known medicinal agents. We are developing a conceptually novel approach to chemical synthesis that takes advantage of the clean, renewable energy in sunlight to construct complex, structurally unique molecules that may serve as templates for the discovery of the next generation of disease-fighting drugs.